AGRN Gene Mutation Leads to Congenital Myasthenia Syndromes: A Pediatric Case Report and Literature Review

2020 ◽  
Vol 51 (05) ◽  
pp. 364-367
Author(s):  
Siyi Gan ◽  
Haiyan Yang ◽  
Ting Xiao ◽  
Zou Pan ◽  
Liwen Wu
Keyword(s):  
Gene Mutation ◽  
Muscle Weakness ◽  
Motor Development ◽  
Neuromuscular Junctions ◽  
Age Of Onset ◽  
Lower Limbs ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Congenital Myasthenia

AbstractThe congenital myasthenia syndromes (CMS) are a group of autosomal recessive or autosomal dominant diseases that affect neuromuscular junctions. CMS caused by AGRN mutations is very uncommon typically characterized by ptosis, mild weakness, and proximal limb weakness. We report the case of an 8-year-old female who exhibited the onset of motor development retardation from infancy and slow progression to proximal muscle weakness. Repeated nerve stimulation at 3 Hz showed a clear decrement with 17%. Whole exon sequencing showed an AGRN gene compound heterozygous mutation (c.5009C >T and c.5078T > C). She was treated with salbutamol but without improvement. Then pseudoephedrine was adapted as a treatment choice and obtained remarkable curative effect. We have summarized and analyzed 12 patients who have been reported in the literature. An early age of onset and muscle weakness in the lower limbs are the main feature of an early AGRN gene mutation. Both types of AGRN-related CMS respond favorably to ephedrine. This is the first report showing that pseudoephedrine is effective as a choice for the treatment of AGRN-related CMS.

scholarly journals Spectrum of clinical manifestation of methylmalonic acidemia and homocystinuria in a family of six siblings: novel combination of transcobalamin receptor defect (CD320) and cblC deficiency (MMACHC)

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nadia Waheed ◽  
Zafar Fayyaz ◽  
Ahmad Imran
Keyword(s):  
Age Of Onset ◽  
Megaloblastic Anemia ◽  
Visual Disturbance ◽  
Methylmalonic Acidemia ◽  
Response To Treatment ◽  
Compound Heterozygous Mutation ◽  
Global Developmental Delay ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Vascular Events

Abstract Background Methylmalonic acidemia with homocystinuria is caused by a rare inborn error of vitamin B12 (cobalamin) metabolism. There are four complementation classes of cobalamin defects cblC, cblD, cblF, and cblJ that are responsible for combined methylmalonic acidemia and homocystinuria. Case presentation We report a case of a Pakistani family composed of six children diagnosed with methylmalonic acidemia and homocystinuria (MMA + HCU). Mutation analysis of siblings revealed a variable combination of c.394C>T mutation in the MMACHC gene and c.262_264del in CD320 gene. All siblings had variable age of onset, initial symptomatology, the severity of disease, and response to treatment. The maximum age of presentation was 6.5 years and the minimum age was at birth. The spectrum of symptoms ranged from a subtle learning disability to global developmental delay within the same family. None of them had a seizure disorder, megaloblastic anemia, visual disturbance, and vascular events.CD320 defect itself is very rare, and only 12 cases have been reported so far. We report six cases, four of them had homozygous MMACHC variant c.394C>T and the other two had heterozygous MMACHC mutations in c.394C>T and c.262_264del in CD 320 genes. To date, neither such case has been reported in the literature or this compound heterozygous mutation. Conclusion Our case report emphasizes that the diagnosis of inherited metabolic disorder in a child obviates the need to screen all siblings for the same disorder.

scholarly journals Case Report: Further Delineation of Neurological Symptoms in Young Children Caused by Compound Heterozygous Mutation in the PIEZO2 Gene

2021 ◽  
Vol 12 ◽  
Author(s):  
Magdalena Klaniewska ◽  
Maria Jedrzejowska ◽  
Malgorzata Rydzanicz ◽  
Justyna Paprocka ◽  
Mateusz Biela ◽  
...  
Keyword(s):  
Motor Development ◽  
Genetic Diagnosis ◽  
Hip Dislocation ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Pathogenic Variants ◽  
Cognitive Delay ◽  
Somatosensory Neurons

PIEZO2 protein is a unique ion channel that converts mechanical impulses into cellular signals in somatosensory neurons and is involved in various mechanotransduction pathways. The recessive PIEZO2 loss-of-function pathogenic variants are associated with distal arthrogryposis with impaired proprioception and touch (DAIPT). Here we present three new DAIPT patients. The genetic diagnosis was established by exome sequencing and let us to identify 6 novel loss-of-function PIEZO2 variants: four splicing (c.1080+1G>A, c.4092+1G>T, c.6355+1G>T, and c.7613+1G>A), one nonsense (c.6088C>T) and one frameshift variant (c.6175_6191del) for which mosaic variant was identified in proband's mother. All patients presented typical symptoms at birth, with congenital contractures, bilateral hip dislocation/dysplasia, generalized hypotonia, transient feeding and difficulties. Two were afflicted by transient respiratory insufficiency. In all children motor development was severely delayed. In one patient, severe cognitive delay was also observed. Moreover, among the cases described by us there is the youngest diagnosed child to date.

Clinical and Genetic Analysis of a Compound Heterozygous Mutation in the Thyroglobulin Gene in a Chinese Twin Family With Congenital Goiter and Hypothyroidism

2012 ◽  
Vol 15 (1) ◽  
pp. 126-132 ◽  
Author(s):  
Shiguo Liu ◽  
Shasha Zhang ◽  
Wenjie Li ◽  
Aiqing Zhang ◽  
Fengguang Qi ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Congenital Hypothyroidism ◽  
High Performance ◽  
Stop Codon ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Chinese Han ◽  
Congenital Goiter ◽  
Normal Controls

Mutations in the thyroglobulin (TG) gene, which has an estimated incidence of approximately 1 in 100,000 new-borns, cause autosomal recessive congenital hypothyroidism. The mutational spectrum of the TG gene and the phenotype–genotype correlations have not yet fully been established. We report a compound heterozygous mutation in the TG gene in a Chinese twin family with congenital goiter and hypothyroidism. We also describe the gene mutation associated with the genotype–phenotype of these children with congenital goiter and hypothyroidism. The whole coding sequence of the TG gene was analyzed by direct sequence, and the identified changes in the sequence were tested for benign polymorphism by denaturing high-performance liquid chromatography screening of the mutation and sequencing 200 chromosomes from normal controls. Analysis of the TG gene of the affected twin revealed a compound heterozygous mutation, including a novel missense mutation G2687A, which is predicted to result in a glutamine to arginine substitution at codon 877, and a known nonsense mutation C7006T, predicted to result in an arginine to stop codon at codon 2317. Analysis of 200 normal chromosomes did not identify the same change in healthy subjects. This is the first report of a TG gene mutation in the Chinese Han population. Our study provides further evidence that mutations in the TG gene cause congenital goiter and hypothyroidism, demonstrates genetic heterogeneity of the mutation, and increases our understanding of phenotype–genotype correlations in congenital hypothyroidism.

scholarly journals A Novel Compound Heterozygous Mutation in ABCB4 Gene Leading to Cholelithiasis, Progressive Familial Intrahepatic Cholestasis (Type 3), and Cirrhosis in a Child

2020 ◽  
Vol 10 (01) ◽  
pp. e134-e136
Author(s):  
Nida Mirza ◽  
Smita Malhotra ◽  
Anupam Sibal
Keyword(s):  
Intrahepatic Cholestasis ◽  
Gall Stone ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Initial Symptom ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Presenting Symptoms ◽  
Abcb4 Gene ◽  
Type 3

AbstractProgressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive disorders of childhood which presents with intermittent or progressive episodes of cholestasis, with jaundice and pruritus as most common presenting symptoms. PFIC type 3 occurs due to mutations in the ABCB4 gene, mutation in this gene has wide spectrum of features which include intrahepatic stones, cholelithiasis, PFIC type 3, and intrahepatic cholestasis of pregnancy. Here, we are reporting a peculiar case of young male adolescent with novel variant compound heterozygote missense mutation in ABCB4 gene who had gall stone as initial symptom, followed by symptoms of PFIC and eventually decompensated chronic liver disease.

scholarly journals Leptin Receptor Compound Heterozygosity in Humans and Animal Models

2021 ◽  
Vol 22 (9) ◽  
pp. 4475
Author(s):  
Claudia Berger ◽  
Nora Klöting
Keyword(s):  
Food Intake ◽  
Animal Models ◽  
Leptin Receptor ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Compound Heterozygosity ◽  
Therapy Options ◽  
Obese Phenotype ◽  
Deficient Mice

Leptin and its receptor are essential for regulating food intake, energy expenditure, glucose homeostasis and fertility. Mutations within leptin or the leptin receptor cause early-onset obesity and hyperphagia, as described in human and animal models. The effect of both heterozygous and homozygous variants is much more investigated than compound heterozygous ones. Recently, we discovered a spontaneous compound heterozygous mutation within the leptin receptor, resulting in a considerably more obese phenotype than described for the homozygous leptin receptor deficient mice. Accordingly, we focus on compound heterozygous mutations of the leptin receptor and their effects on health, as well as possible therapy options in human and animal models in this review.

scholarly journals Novel compound heterozygous mutation in SACS gene leads to a milder autosomal recessive spastic ataxia of Charlevoix‐Saguenay, ARSACS , in a Finnish family

2016 ◽  
Vol 4 (12) ◽  
pp. 1151-1156 ◽  
Author(s):  
Johanna Palmio ◽  
Mikko Kärppä ◽  
Peter Baumann ◽  
Sini Penttilä ◽  
Jukka Moilanen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Spastic Ataxia
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